Hypoglycemic compositon containing acacia bark derivative

ABSTRACT

It is intended to provide a composition having an excellent hypoglycemic action without potential for adverse side effects and the like even if taken for a long period of time. The composition is a hypoglycemic composition containing an acacia bark derivative.

TECHNICAL FIELD

The present invention relates to a hypoglycemic composition derived froma tree belonging to the genus Acacia, and to uses of this hypoglycemiccomposition as a food, an animal feed material, a medicine and aquasi-drug.

BACKGROUND ART

The number of persons exhibiting diabetes or impaired glucose tolerancewhich would be diabetes, has increased in recent years due toWesternization of the diet, a lack of exercise resulting from thedevelopment of transportation facilities and the like. In particular,diabetes causes complications including diabetic neuropathies such asnumbness and pain, cataracts, diabetic retinopathy, arteriosclerosis,diabetic nephropathy or diabetic gangrene, and there are also cases thatultimately lead to death. Accordingly, the treatment thereof can be saidto be extremely important.

Although improvement of lifestyle is desired for the prevention ortreatment of diabetes, this cannot always be easily achieved.

In addition, although the treatment for diabetes involves methods forregulating the level of insulin in the blood by an insulin injection oran oral administration of hypoglycemic agents, these methods areaccompanied by adverse side effects, while a diet therapy and anexercise therapy have the problems of being difficult for a patient tocomply with them.

Amidst these circumstances, attempts have been made to prevent or treatdiabetes and hyperglycemia by using natural ingredients which have awide range of actions and no potential for adverse side effects and thelike even if taken for a long period. For example, Patent Document 1describes a therapeutic and preventive agent for hyperglycemiacontaining an extract of a plant belonging to the genus Bidens, PatentDocument 2 describes a composition for improving hyperglycemia having asan active ingredient a dried acetic acid fermented product of theAmaranthus seed, Patent Document 3 describes a preventive and/ortherapeutic agent for a diabetic disease containing as an activeingredient Sargassum horneri or a treated product thereof, PatentDocument 4 describes a fucoidan-based health food which suppresseshyperglycemia and maintains blood sugar at a low level, and PatentDocument 5 describes a food for persons with hyperglycemia containingolive leaves or an extract thereof.

On the other hand, with respect to acacia, acacia honey is known, andtannin which is extracted from bark thereof is known to be able to beused as a tanning agent or a wood adhesive, while more recently,extracts of genus Acacia have been disclosed to have selectiveinhibitory effects on COX-2 (Patent Document 6), and bark of genusAcacia has been disclosed to have active oxygen eliminating effects(Patent Document 7) and skin whitening effects due to the effect ofinhibiting tyrosinase activity (Patent Document 8). However, acacia barkand polyphenols derived from acacia bark have heretofore not been knownto have a hypoglycemic action.

[Patent Document 1] JP2004-323362A

[Patent Document 2] JP7-138178A

[Patent Document 3] JP2004-217559A

[Patent Document 4] JP2004-24054A

[Patent Document 5] JP2002-10753A

[Patent Document 6] JP2004-532811A

[Patent Document 7] JP2004-352639A

[Patent Document 8] JP10-025238A

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention

An object of the present invention is to provide a composition having anexcellent hypoglycemic action without potential for adverse side effectsand the like even if taken for a long period of time.

Means for Solving the Problems

As a result of conducting extensive studies to solve the above problems,the inventors of the present invention found that an acacia barkderivative has an action of lowering blood sugar levels to be useful forthe prevention or treatment of a hyperglycemic disease such as diabetes,thereby leading to the completion of the present invention.

Namely, the present invention relates to a hypoglycemic compositioncontaining an acacia bark derivative(s).

In addition, the present invention also relates to a method forpreventing or treating a hyperglycemic disease such as diabetes using anacacia bark derivative(s).

Moreover, the present invention relates to a method for using an acaciabark derivative(s) for producing a composition for preventing ortreating a hyperglycemic disease such as diabetes.

Effects of the Invention

According to the present invention, a composition having a hypoglycemicaction can be provided.

Moreover, according to the present invention, a composition is providedwhich is safe and has less potential for adverse side effects and thelike even if taken for a long period of time.

BEST MODE FOR CARRYING OUT THE INVENTION

There are no particular limitations on the acacia bark derivative ableto be used in the present invention provided that it is obtained byusing as a raw material bark of a tree belonging to the genus Acacia(the tree is referred to as “acacia” or “genus Acacia” hereinafter),examples of which derivatives include a strip and a powder of acaciabark, and a suspension thereof, an extract such as a liquid extract, aconcentrated liquid extract and a powdered extract of acacia bark, and apurified product obtained by purifying these extracts. The extract ofacacia bark and particularly acacia bark polyphenols are preferable forproduction of excellent hypoglycemic activity.

In the present invention, only a single form of these acacia barkderivatives may be used, or alternatively two or more forms thereof maybe used in combination.

Although there are no particular limitations on acacia able to be usedin the present invention so long as it is a tree belonging to the genusAcacia, with respect to obtaining an acacia bark derivative having anexcellent hypoglycemic action, bark of the genus Acacia selected fromthe group consisting of scientific name: Acacia mearnsii De Wild.(generic name: black wattle), scientific name: Acacia mangium Willd.(generic name: acacia mangium), scientific name: Acacia dealbata Link,scientific name: Acacia decurrens Willd. and scientific name: Acaciapycnantha Benth. are preferable, while Acacia mearnsii De Wild. andAcacia mangium Willd. are particularly preferable.

In the present invention, only a single form of these acacia bark may beused, or alternatively two or more forms thereof may be used incombination.

The aforementioned acacia bark can normally be obtained by cutting downan acacia tree, pealing off only bark and then drying the bark morepreferably by sun-drying.

Bark of acacia is comprised of an outer bark and a somewhat fibrousinner bark, and when dried to a moisture content of about 20% or less,can be easily finely pulverized with a size reduction mill such as ahammer mill. In the present invention, both the outer bark and innerbark of the genus Acacia may be used together or either one may be usedalone as the acacia bark.

The aforementioned strip of acacia bark can be obtained in accordancewith commonly used methods by pulverizing the acacia bark to a suitablesize.

In addition, although the aforementioned powder of acacia bark can beobtained by pulverizing the acacia bark into a powder in accordance withcommonly used methods, in particular, the particle diameter of theresulting powder is preferably 100 μm or less and particularlypreferably 50 to 70 μm. Powder fractionation can be carried out bypulverizing the bark dried to a moisture content of 20% or less to asuitable size such as a particle diameter of about 1.6 mm or less, andthen classifying the resulting powder with a vibrating screen or thelike to obtain the required powder.

The aforementioned extract of acacia bark can be obtained by extractionfrom the acacia bark in accordance with commonly used methods. In orderto obtain an extract of acacia bark having an excellent hypoglycemicaction, it is preferably extracted from the acacia bark with an alcoholor a polar solvent.

Ethanol, etc. can be used as the alcohol, and water, etc. can be used asthe polar solvent, and these solvents may be used singly or incombination of two or more kinds as necessary. A mixed solvent of waterand the alcohol such as ethyl alcohol is particularly preferable forproduction of an excellent hypoglycemic action.

Moreover, the extraction procedure may be carried out a number of timesusing the same or different solvents.

In terms of obtaining an extract having an excellent hypoglycemicaction, an extract which is obtained from the acacia bark by extractionwith water or hot water, and then further extraction from the resultingextract with ethanol may be used.

Although the extraction is carried out by adding the solvent to a strip,a powder or the like of the acacia bark followed by stirring asnecessary, there are no particular limitations on temperature, time orsolid-liquid ratio. In the case of using water as the solvent, theextraction may also be carried out with hot water. The resulting liquidextract may be freeze-dried or spray-dried directly, or may befreeze-dried or spray-dried after concentrating under reduced pressure.The resulting extract can be in various forms, such as a liquid extract,solution, powder, concentrate or paste, and can be used in a wide rangeof forms as necessary.

Moreover, the acacia bark extract of the present invention obtained inany of these forms can be used directly as a hypoglycemic composition,or a purified product obtained by purifying the extract as necessary canalso be used as a hypoglycemic ingredient.

In the present invention, ingredients contained in bark of the genusAcacia are also examples of the acacia bark derivatives. Examples ofsuch ingredients are the acacia bark polyphenols. The acacia barkpolyphenols are particularly preferable ingredients since they produceexcellent hypoglycemic action.

The acacia bark polyphenols of the present invention refer to a type ofcondensed tannins in the form of polymers in which flavanols having as abasic skeleton flavan-3-ol such as (−)-fisetinidol, (−)-robinetinidol,(+)-catechin and (+)-gallocatechin are linked by C4-C8 or C4-C6 bonds.Here, the molecular weights of such condensed tannins are preferably 300to 3000 and particularly preferably 500 to 3000. The acacia barkpolyphenols used in the present invention can be obtained from thepowder, etc. of the acacia bark by extracting with hot water aspreviously described.

In addition, examples of commercially available acacia bark polyphenolsinclude MIMOSA ME POWDER, MIMOSA MS POWDER, MIMOSA GS POWDER, MIMOSA FSPOWDER, MIMOSA WS POWDER, MIMOSA RG POWDER, MIMOSA RN POWDER, MIMOSA DKPOWDER, MIMOSA AL POWDER, MIMOSA CR POWDER and GOLDEN MIMOSA POWDER (allregistered trademarks) which are manufactured by Mimosa CentralCo-operative Ltd., and the like.

Although the composition of the present invention may be the acacia barkderivative(s) such as the acacia bark, the extract(s) thereof, thepurified product(s) thereof or the acacia bark polyphenol(s) per se, itmay also contain other substance(s) having a hypoglycemic action, suchas black vinegar, onion extract or yacon. Yacon and particularly Yacontea are particularly preferably contained since they produce excellenthypoglycemic actions due to synergistic effects.

Although the composition of the present invention may be the acacia barkderivative(s) such as the acacia bark, the extract(s) thereof, thepurified product(s) thereof or the acacia bark polyphenol(s) per se, itmay contain vehicles, sweeteners, sour flavorings, thickeners,fragrances, pigments, emulsifiers, and other materials which areordinarily used in foods, so long as they do not undermine the effectsof the present invention.

The composition according to the present invention can be used as a foodor an animal feed material, for example, as a health food, a functionalfood, a health supplement food, a food for specified health use, abeauty food or a nutritional supplement food (supplement) for purposessuch as preventing or eliminating a disease accompanied by elevatedblood sugar levels such as diabetes or hyperglycemia. For example, thesefoods or animal feed material may also be in the form of a beverage suchas tea or juice; ice cream, jelly, candy, chocolate or chewing gum, etc.In addition, they may also be in the form of liquids, powders, granules,capsules or tablets. Here, animals fed using the animal feed materialinclude all animals requiring the prevention or elimination of diseasesaccompanied by elevated blood sugar levels, and include pets, livestockor animals bred at zoos, etc.

In addition, the composition according to the present invention can beused as a medicine or a quasi-drug for the prevention, elimination,treatment or the like of a disease accompanied by elevated blood sugarlevels such as diabetes or hyperglycemia. These medicine and drug can beadministered, for example, orally in the form of tablets, coatedtablets, sugar coated pills, hard or soft gelatin capsules, liquids,emulsions or suspensions.

There are no particular limitations on an ingested amount of thecomposition according to the present invention, and the ingested amountcan be suitably selected depending on the dosage form as well as theage, body weight and symptoms of an ingesting person such as a user orpatient, or an ingesting animal. For example, it is desired that theingesting person or ingesting animal orally ingests an amount of theacacia bark polyphenol(s) ranging from 0.001 to 1 g, preferably from0.001 to 0.5 g and more preferably from 0.005 to 0.1 g per 1 kg of bodyweight per day in terms of the amount of active ingredient, since itproduces an excellent hypoglycemic action.

The duration of ingestion can be arbitrarily determined depending on theage and symptoms of the user or patient.

Although the following provides a more detailed explanation of thepresent invention through examples thereof, the present invention is notlimited thereto.

Examples

Although the following provides a more detailed explanation of thepresent invention through production examples, test examples andformulation examples thereof, the present invention is not limitedthereto. In particular, although the following examples are indicatedwithout making a distinction between the outer bark and inner bark ofthe acacia bark of the present invention, the outer bark can beseparated from the inner bark and each can also be used, separately.

In the following production examples, test examples and the like, eachacacia of the present invention is indicated with numbers shown inparentheses after each scientific name. For example, acacia known by thescientific name of Acacia mearnsii De Wild. is indicated as Acacia No.1.

Scientific name: Acacia mearnsii De Wild. (No. 1), scientific name:Acacia mangium Willd. (No. 2), scientific name: Acacia dealbata Link(No. 3), scientific name: Acacia decurrens Willd. (No. 4), scientificname: Acacia pycnantha Benth. (No. 5).

In addition, percentages (%) refer to percent by weight (wt %) unlessspecifically indicated otherwise.

Production Example 1 Acacia Bark Powder

Bark of Acacia No. 1 was dried to a moisture content of 20% or less andafter pulverizing the dried bark in a hammer mill to a powder having aparticle diameter of 1.6 mm or less (the powder passing through a 10mesh Tyler screen), the powder was further classified with a vibratingscreen to obtain a fine powder having a particle diameter of 63 μm orless (passing through a 250 mesh screen).

Fine powders each having a particle diameter of 63 μm or less weresimilarly obtained by pulverizing bark of the remaining four types ofacacia namely Acacia No. 2 to Acacia No. 5. Although there were somedifferences in the efficiency by which the fine powder passed throughthe 250 mesh screen depending on the type, all of the target finepowders were able to be obtained.

Production Example 2 Acacia Bark Extract

Bark of each Acacia No. 1 to 5 of the present invention was dried to amoisture content of 20% or less and after pulverizing the dried bark ina hammer mill to a powder having a particle diameter of 1.6 mm or less,five times the amount of hot water were added to 100 g of the driedpulverized bark followed by extraction for 15 minutes after boiling, andthen filtering using a 10 to 20 μm filter. The resulting filtrate wasspray-dried in a spray dryer to obtain 40 g of each bark extract.

The bark extracts are hereinafter indicated as Acacia Hot Water ExtractsNos. 1 to 5, respectively.

Production Example 3 Acacia Bark Extract

Acacia bark of the present invention was dried to a moisture content of20% or less and after pulverizing the dried bark in a hammer mill to apowder having a particle diameter of 1.6 mm or less, five times theamount of ethanol were added to 100 g of the dried pulverized barkfollowed by extracting for 15 minutes while refluxing after boiling, andthen filtering using a 10 to 20 μm filter. After evaporating the ethanolfrom the resulting filtrate, the concentrate was spray-dried in a closedspray dryer to obtain 40 g of bark extract (to be indicated hereinafterin the manner of Acacia Ethanol Extract No. 1).

Acacia Ethanol Extracts Nos. 1 to 5 were obtained in the same manner.

Production Example 4 Acacia Bark Extract

Three times the amount of ethanol were added to 10 g of the acacia hotwater extract obtained in Production Example 2 followed by extractionfor 15 minutes while refluxing after boiling, and then filtering using a10 to 20 μm filter. The ethanol was evaporated from the resultingfiltrate, water was added thereto, and then freeze-dried to obtain 9 gof extract (to be indicated hereinafter in the manner of Acacia HotWater Extract Ethanol Fraction No. 1).

Acacia Hot Water Extract Ethanol fractions Nos. 1 to 5 were obtained inthe same manner.

Test Example 1 Blood Sugar Elevation Inhibition Test (1) 1. Test Method

Feed containing 50 of Acacia Hot Water Extract No. 1 described inProduction Example 2 was fed for 28 days to type II diabetes model mice(C57BLKS/J Iar-+Lepr^(db)/+Lepr^(db), males, age 7 weeks). A controlgroup was fed ordinary commercially available feed.

Blood sugar levels, urine glucose levels and plasma insulin levels weremeasured before the start of dosing and on the day after the final dayof dosing. The mice were fasted starting on the day before measurementdays. Blood sugar levels and urine glucose levels were measured with theFreeStyle Kissei Meter (C-D036-01014, Kissei Pharmaceutical Co., Ltd.).Insulin levels were measured with the Insulin Mouse T (Shibayagi Co.,Ltd.).

Each of the resulting measured values was expressed as the mean±standarderror. Testing for the presence of a significant difference from thecontrol group was carried out using the Student's t-test in the presenceof a uniform distribution as determined with the F test, and carried outusing the Aspin-Welch t-test in the absence of a uniform distribution asdetermined with the F test. The level of significance was indicated as5% or 1%.

2. Test Results

The results are shown in the following Tables 1 and 2. None of the micedied or demonstrated abnormalities in general condition.

TABLE 1 Changes in Blood Sugar Levels and Urine Glucose Levels Bloodsugar level (mg/dL) Urine glucose level (mg/dL) No. of Day 29 afterstart Day 29 after start Dose group animals Before dosing of dosingBefore dosing of dosing Control group 7 288.4 ± 18.0 342.1 ± 36.7  524.1± 33.6 464.1 ± 332.0 Acacia Hot Water Extract 7 302.4 ± 23.4 116.1 ±13.9** 407.3 ± 55.2 19.4 ± 3.3  No. 1 dose group (66.1%) (95.8%) ( ):Rate of decrease (%) versus control group. **Comparison with controlgroup. It shows P < 0.01.

TABLE 2 Changes in Insulin Levels No. of Insulin level (ng/mL) Dosegroup animals Day 29 after start of dosing Control group 7 2.7 ± 0.5 Acacia Hot Water 7 5.3 ± 0.8* Extract No. 1 (96.3%) dose group ( ): Rateof increase (%) versus control group. *Comparison with control group. Itshows P < 0.05.

On the basis of the above results, the acacia bark polyphenols wereobserved to have the effect of inhibiting the elevation of blood sugarlevels attributable to diabetes by lowering blood sugar levels as wellas diminish symptoms associated with diabetes.

Test Example 2 Blood Sugar Elevation Inhibition Test (2) 1. Test Method

Feed samples respectively containing 0.5, 1.5 and 5.0% of Acacia HotWater Extract No. 1 described in Production Example 2 were fed for 28days to type II diabetes model mice (BKS.Cg-+Lepr^(db)/+Lepr^(db)/Jcl,males, age 7 weeks). A control group was fed ordinary commerciallyavailable feed.

Each parameter was measured in the same manner as Test Example 1.Furthermore, blood sugar and urine glucose levels were measured beforethe start of dosing, on day 14 after the start of dosing and on the dayafter the final day of dosing. In addition, weekly water and foodconsumption were measured once a week followed by the calculation of theamounts consumed per day. Glycosylated hemoglobin levels were measuredon the day after the final day of dosing by immunoinhibitionnephelometry.

The resulting measured values were expressed as the mean±standarddeviation. Testing for the presence of a significant difference from thecontrol group was carried out using Dunnett's multiple comparison test.The level of significance was indicated as 5% or 1%.

2. Test Results

The results are shown in the following Tables 3 to 7. None of the micedied or demonstrated abnormalities in general condition.

TABLE 3 Food Consumption (g/day) No. of Measurement weeks Dose groupanimals Week 1 Week 2 Week 3 Week 4 Control group 7 6.1 ± 0.8 6.8 ± 0.45.9 ± 0.4  6.0 ± 0.6  Acacia Hot Water Extract 7 6.1 ± 1.3 7.4 ± 0.4 7.6 ± 0.3** 7.3 ± 0.1* No. 1 0.5% dose group Acacia Hot Water Extract 75.7 ± 0.7 6.8 ± 0.9 7.0 ± 0.7* 7.3 ± 0.8* No. 1 1.5% dose group AcaciaHot Water Extract 7 5.8 ± 1.8 6.8 ± 1.2 7.1 ± 1.3* 7.3 ± 1.4* No. 1 5.0%dose group *Comparison with control group. It shows P < 0.05.**Comparison with control group. It shows P < 0.01.

TABLE 4 Water Consumption (mg/day) No. of Measurement weeks Dose groupanimals Week 1 Week 2 Week 3 Week 4 Control group 7 10.9 ± 5.2  12.5 ±6.2 12.4 ± 8.2  15.2 ± 10.0 Acacia Hot Water Extract 7 9.2 ± 0.6 11.2 ±0.5 13.4 ± 1.6 15.5 ± 2.4 No. 1 0.5% dose group (15.6%) (10.4%) (−8.1%)(−2.0%) Acacia Hot Water Extract 7 7.7 ± 1.6  8.9 ± 2.2 10.1 ± 1.7 11.1± 1.4 No. 1 1.5% dose group (29.4%) (28.8%) (18.5%) (27.0%) Acacia HotWater Extract 7  3.3 ± 0.3**   4.3 ± 0.5**   4.6 ± 0.3**   4.5 ± 0.6**No. 1 5.0% dose group (69.7%) (65.6%) (62.9%) (70.4%) ( ): Rate ofdecrease (%) versus control group. **Comparison with control group. Itshows P < 0.01.

TABLE 5 Blood Sugar Levels (mg/dL) Measurement days No. of Day 14 afterstart Day 29 after start Dose group animals Before dosing of dosing ofdosing Control group 7 272.7 ± 22.5 293.9 ± 47.9 425.4 ± 79.0 Acacia HotWater 7 273.1 ± 23.4 281.4 ± 20.4 376.0 ± 67.2 Extract No. 1 0.5% (4.3%) (11.6%) dose group Acacia Hot Water 7 273.3 ± 20.1 260.0 ± 46.1 333.7 ± 54.8* Extract No. 1 1.5% (11.5%) (21.6%) dose group Acacia HotWater 7 269.3 ± 16.1 248.3 ± 37.6  160.3 ± 47.7** Extract No. 1 5.0%(15.5%) (62.3%) dose group ( ): Rate of decrease (%) versus controlgroup *Comparison with control group. It shows P < 0.05. **Comparisonwith control group. It shows P < 0.01.

TABLE 6 Urine Glucose Levels (mg/dL) Measurement days No. of Day 14after start Day 29 after start Dose group animals Before dosing ofdosing of dosing Control group 7 108.1 ± 11.0 514.9 ± 381.9  651.4 ±356.3 Acacia Hot Water 7 117.3 ± 29.7 140.6 ± 30.4** 659.0 ± 250.1Extract No. 1 0.5% (72.7%) (−1.2%) dose group Acacia Hot Water 7 110.6 ±9.8  179.0 ± 129.2* 527.4 ± 341.0 Extract No. 1 1.5% (65.2%) (19.0%)dose group Acacia Hot Water 7 105.0 ± 1.2  110.4 ± 5.9**  108.0 ± 8.0**Extract No. 1 5.0% (78.6%) (83.4%) dose group ( ): Rate of decrease (%)versus control group *Comparison with control group. It shows P < 0.05.**Comparison with control group. It shows P < 0.01.

TABLE 7 Insulin and Glycosylated Hemoglobin Levels No. of InsulinGlycosylated hemoglobin Dose group animals (ng/mL) (g/dL) Control group7 2.6 ± 1.3 1.0 ± 0.3 Acacia Hot Water 7 1.5 ± 0.4 1.1 ± 0.1 Extract No.1 0.5% (−42.3%)   (−10.0%)   dose group Acacia Hot Water 7 3.4 ± 2.0 1.0± 0.2 Extract No. 1 1.5% (30.8%)  (0.0%) dose group Acacia Hot Water 74.0 ± 0.9  0.5 ± 0.1** Extract No. 1 5.0% (53.8%) (50.0%) dose group (): Rate of increase (%) versus control group for insulin, or rate ofdecrease (%) versus control group for glycosylated hemoglobin**Comparison with control group. It shows P < 0.01.

According to the above results, since insulin levels were observed toincrease while water consumption, blood sugar levels, urine glucoselevels and glycosylated hemoglobin levels were observed to decreasedependent on the dose of Acacia Hot Water Extract No. 1, symptoms ofdiabetes such as hypoinsulinemia, polyposia and hyperglycemia werethought to be diminished by the ingestion of the acacia barkpolyphenols.

Test Example 3 Mutagenicity Test

A mutagenicity test was conducted in compliance with Ministry of Health,Labor and Welfare Notification No. 77 (Sep. 1, 1988). As a result oftesting with test substance (Acacia Hot Water Extracts Nos. 1 to 5 ofProduction Example 2) at doses of 156 to 5,000 μg/plate, there were noincreases in the numbers of revertant colonies for any of the bacterialstrains.

Test Example 4 Micronucleus Test

The ability to induce micronuclei was investigated in vivo in accordancewith ordinary methods. Acacia Hot Water Extract No. 1 was orallyadministered twice at 24-hour intervals at daily doses of 2,000, 1,000and 500 mg/kg to male ICR mice followed by the preparation ofmicronucleus specimens 24 hours after the final dosing.

Acacia Hot Water Extract No. 1 did not demonstrate positive results atany of the dose levels. In addition, there were no constant fluctuationsin the simultaneously observed ratio of total polychromatic erythrocytesto total erythrocytes, and inhibition of erythrocyte proliferation wasnot observed in comparisons with a negative control group.

Test Example 5 Mouse Acute Toxicity Study (Oral Administration)

An acute oral dose toxicity study was conducted using male and femaleICR mice in compliance with OECD (Guidelines for the Testing ofChemicals, 401, 1987). As a result, the LD₅₀ value of Acacia Hot WaterExtract No. 1 was 4,468 mg/kg among males and 3,594 mg/kg among females.

Similar results were obtained in the above study for Acacia Hot WaterExtracts Nos. 2 to 5 of Production Example 2.

Test Example 6 Rat Repeated Dose Toxicity Study (Oral Administration)

A 13-week repeated dose toxicity study was conducted using rats inaccordance with ordinary methods. Mixed feed containing 0.5, 1.5 and5.00 of Acacia Hot Water Extract No. 1 was fed to male and female Slc:SDrats.

As a result, none of the rats died or demonstrated abnormalities inexaminations, including general condition.

Test Example 7 Human Single Dose Study

Five healthy adult males age 32 to 43 years were given 1500 mg of AcaciaHot Water Extract No. 1 (12 tablets of Formulation Example 4 describedbelow). Although general examinations, hematology tests, bloodbiochemistry tests and urinalyses were performed on the subjects beforeingestion, 3 hours after ingestion, 8 hours after ingestion, 24 hoursafter ingestion and 1 week after ingestion, there were no clinicallysignificant fluctuations in test values. There were also no adverseevents attributable to the tablets.

Test Example 8 Human 4-Week Continuous Dosing Study

Twenty-five healthy adult males age 23 to 44 years were given Acacia HotWater Extract No. 1 of Formulation Example 4 described below at 750mg/day (6 tablets of Formulation Example 4) and 1000 mg/day (8 tabletsof Formulation Example 4) for 4 weeks each.

General examinations, hematology tests and urinalyses were performed onthe subjects of each group before ingestion, 2 weeks after ingestion, 4weeks after ingestion and 2 weeks following completion of ingestion.There were no clinically significant fluctuations in test values. Therewere also no adverse events.

Formulation Example 1 Preparation of Internal Medication

An internal medication having the composition indicated below wasprepared using the acacia bark Hot Water Extract Ethanol Fraction ofProduction Example 4.

Extract fraction of Production Example 4 1.0 (wt %) Lactose 30.0Cornstarch 60.0 Crystalline cellulose 8.0 Polyvinyl pyrrolidone 1.0Total 100.0

Formulation Example 2 Preparation of Pet Food

A pet food having the composition indicated below was prepared using theacacia bark Hot Water Extract of Production Example 2.

Extract of Production Example 2 1.0 (wt %) Oatmeal 88.0 Starch 5.0 Salt2.5 Whole egg 3.0 Flavoring 0.5 Total 100.0

Formulation Example 3 Preparation of Tablets (Confections)

Tablets (confections) having the composition indicated below wereprepared using the acacia bark Hot Water Extract Ethanol Fraction ofProduction Example 4.

Extract fraction of Production Example 4 1.0 (wt %) Citric acid 1.0Powdered skim milk 15.0 Sucrose ester 1.0 Flavoring 0.5 Powdered sugar20.0 Lactose 61.5 Total 100.0

Formulation Example 4 Preparation of Tablets

Tablets having the composition indicated below were prepared usingAcacia Bark Hot Water Extract No. 1 of Production Example 2.

Acacia Bark Hot Water Extract No. 1 of 125 (mg) Production Example 2Sucrose ester 9 Lactose 166 Total 300

INDUSTRIAL APPLICABILITY

The hypoglycemic composition of the present invention can be used as amedicine or a quasi-drug; or as a food such as a health food, a healthsupplement food, a food for specified health use or a nutritionalsupplement food; or as an animal feed material, for use in eliminatingand/or preventing and/or treating diseases accompanied by elevated bloodsugar levels.

Examples of the aforementioned diseases accompanied by elevated bloodsugar levels include not only diabetes such as type I or type IIdiabetes and hyperglycemia, but also diseases caused by diabetes orhyperglycemia, including complications such as diabetic hyperlipemia,diabetic osteoporosis, symptoms of weight loss caused by diabetes,symptoms of fluctuations in blood mineral concentrations due todiabetes, diabetic neuropathies such as numbness or pain, cataracts,arteriosclerosis, peripheral circulatory disorders, diabetic gangrenesuch as gangrene of the lower extremities, diabetic retinopathy ordiabetic nephropathy.

In particular, since the composition of the present invention inhibitselevation of blood sugar levels, it is thought to be able to preventhyperglycemia and even prevent diabetes, thereby making it useful as ahealth food or a food for specified health use.

1. A hypoglycemic composition containing an acacia bark derivative(s).2. The composition according to claim 1, wherein the acacia bark is atleast one bark selected from the group consisting of Acacia mearnsii DeWild, Acacia mangiurn Willd, Acacia dealbata Link, Acacia decurrensWilld and Acacia pycnantha Benth.
 3. The composition according to claim1, wherein the acacia bark is bark of Acacia mearnsii De Wild. or Acacianiangium Willd.
 4. The composition according to claim 1, wherein theacacia bark derivative(s) is an extract(s) of acacia bark.
 5. Thecomposition according to claim 1, wherein the acacia bark derivative(s)is an acacia bark polyphenol(s).
 6. The composition according to claim5, wherein the acacia hark polyphenol(s) is a condensed tannin(s). 7.The composition according to claim 6, wherein the condensed tannin(s)has a molecular weight(s) of 500 to
 3000. 8. The composition accordingto claim 6, wherein the condensed tannin(s) is a polymer(s) of flavanolshaving flavan-3-ol as a basic skeleton.
 9. The composition according toclaim 1, wherein the acacia bark polyphenol(s) is orally ingested by aningesting person or an ingesting animal at 0.001 to 1 g per kg of bodyweight per day in terms of the amount of active ingredient.
 10. Thecomposition according to claim 1, wherein the composition is a food. 11.The composition according to claim 1, wherein the composition is ananimal feed material.
 12. The composition according to claim 1, whereinthe composition is a medicine.
 13. The composition according to claim 1,wherein the composition is a quasi-drug.
 14. A method of treatinghypoglycemia which comprises treating a body in need thereof with acomposition containing an acacia hark derivative(s).
 15. The method oftreating hypoglycemia according to claim 14, wherein the acacia bark isat least one bark selected from the group consisting of Acacia mearnsiiDe Wild, Acacia mangium Willd, Acacia dealbata Link. Acacia decurrensWilld and Acacia pycnantha Benth.
 16. The method of treatinghypoglycemia according to claim 14, wherein the acacia bark is a bark ofAcacia mearnsii De Wild. or Acacia mangium Willd.